Microemulsions strongly promoted the activity of α-bisabolol against different Leishmania species and its skin permeation.

This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.

Exploring the association of serum prolactin with serum glucose levels and clinical findings in a cohort of patients with early rheumatoid arthritis.

BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.

Structural Racism in Newborn Drug Testing: Perspectives of Health Care and Child Protective Services Professionals.

PURPOSE: Black birthing parents and their newborns disproportionately experience newborn drug testing for prenatal substance exposure by health care professionals (HCPs), which contributes to Child Protective Services (CPS) reporting, family separation, and termination of parental rights. This qualitative study aims to interrogate dominant power structures by exploring knowledge, attitudes, and experiences of HCPs and CPS professionals regarding the influence of structural racism on inequities in newborn drug testing practices. METHODS: We conducted semistructured interviews with 30 physicians, midwives, nurses, social workers, and CPS professionals guided by an explanatory framework, and conducted inductive, reflexive thematic analysis. RESULTS: We identified 3 primary themes: (1) levels of racism beyond the hospital structure contributed to higher rates of drug testing for Black newborns; (2) inconsistent hospital policies led to racialized application of state law and downstream CPS reporting; and (3) health care professionals knowledge of the benefits and disproportionate harms of CPS reporting on Black families influenced their decision making. CONCLUSION: Health care professionals recognized structural racism as a driver of disproportionate newborn drug testing. Lack of knowledge and skill limitations of HCPs were barriers to dismantling power structures, thus impeding systems-level change. Institutional changes should shift focus from biologic testing and reporting to supporting the mutual needs of birthing parent and child through family-centered substance use treatment. State and federal policy changes are needed to ensure health equity for Black families and eliminate reporting to CPS for prenatal substance exposure when no concern for child abuse and neglect exists.

Encapsulation of Citrus sinensis essential oil and R-limonene in lipid nanocarriers: A potential strategy for the treatment of leishmaniasis.

Leishmaniases, a group of neglected tropical diseases caused by an intracellular parasite of the genus Leishmania, have significant impacts on global health. Current treatment options are limited due to drug resistance, toxicity, and high cost. This study aimed to develop nanostructured lipid carriers (NLCs) for delivering Citrus sinensis essential oil (CSEO) and its main constituent, R-limonene, against leishmaniasis. The influence of surface-modified NLCs using chitosan was also examined. The NLCs were prepared using a warm microemulsion method, and surface modification with chitosan was achieved through electrostatic interaction. These nanocarriers were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), transmission electron microscopy, and dynamic light scattering (DLS). In vitro cytotoxicity was assessed in L929 and RAW 264.7 cells, and leishmanicidal activity was evaluated against promastigote and amastigote forms. The NLCs were spherical, with particle sizes ranging from 97.9 nm to 111.3 nm. Chitosan-coated NLCs had a positive surface charge, with zeta potential values ranging from 45.8 mV to 59.0 mV. Exposure of L929 cells to NLCs resulted in over 70 % cell viability. Conversely, surface modification significantly reduced the viability of promastigotes (93 %) compared to free compounds. Moreover, chitosan-coated NLCs presented a better IC50 against the amastigote forms than uncoated NLCs. Taken together, these findings demonstrate the feasibility of using NLCs to overcome the limitations of current leishmaniasis treatments, warranting further research.

The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis.

OBJECTIVE: To evaluate the association between psoriasis (PSO), psoriatic arthritis (PsA) and periodontitis (PE), and the Oral Health-Related Quality of Life (OHRQoL) impacts on individuals with psoriatic disease's daily activities compared to the non-psoriatic ones. MATERIALS & METHODS: 296 individuals with psoriatic disease (PSO n = 210, APS n = 86) (cases) and 359 without these diseases (controls) were included. Complete periodontal examinations and collection of variables of interest were performed. The Brazilian version of the Oral Impacts on Daily Performance (OIDP) instrument was applied. RESULTS: The prevalence of PE was higher in PsA (57.0%; OR = 2.67 95%CI 1.65-4.32; p<0.001) than in PSO (34.3%; OR = 1.05 95% CI 0.73-1.51; p<0.001) compared to controls (33.1%). Both PsA and PSO groups showed more sites and teeth with 4-6mm probing depth (PD) and had higher OIDP scores than controls (p<0.001), thus indicating worse self-reported quality of life. PE, PSO+PE and consumption of alcohol/anxiolytics significantly influenced OHRQoL (p<0.05). The influence of periodontal parameters on OHRQoL was observed for the presence of PE; PD >6 mm; clinical attachment level >6 mm; higher plaque index, % sites and teeth with bleeding on probing (p<0.05). CONCLUSION: Negative impacts of PE on the OHRQoL were demonstrated. The ones having PSO and especially PsA and PE presented significantly worse indicators.

Sleep and memory complaints in long COVID: an insight into clustered psychological phenotypes.

This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.

Maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder. / Transtorno do espectro do autismo e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas.

The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.

O presente estudo objetivou investigar a associação entre o TEA e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas. Trata-se de um estudo caso-controle realizado com crianças e adolescentes diagnosticados com TEA e indivíduos neurotípicos. Os dados foram colhidos por meio de entrevista com as mães ou responsáveis. Foram analisadas as variáveis sexo e idade das crianças/adolescentes; idade dos pais; uso de medicamentos antes e durante a gestação; classes de medicamentos usados na gestação; tabagismo materno e paterno; etilismo materno e paterno; uso de drogas ilícitas pelos pais. Para a análise das informações, utilizou-se o modelo de regressão logística, além da razão de chances (OR) bruta e ajustada. Os resultados mostraram que, após os ajustes, foi encontrada associação entre o uso materno na gestação de antitérmicos/analgésicos (OR = 2,26; IC95% 1,29-3,95; p < 0,040) com o TEA. Já o uso de tabaco, álcool e drogas ilícitas materno e paterno, antes e durante a gestação, não apontou relação com o TEA. Os dados encontrados sugerem que existe influência de fatores ambientais no desenvolvimento do TEA.

Transtorno do espectro do autismo e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas / Maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder

Resumo O presente estudo objetivou investigar a associação entre o TEA e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas. Trata-se de um estudo caso-controle realizado com crianças e adolescentes diagnosticados com TEA e indivíduos neurotípicos. Os dados foram colhidos por meio de entrevista com as mães ou responsáveis. Foram analisadas as variáveis sexo e idade das crianças/adolescentes; idade dos pais; uso de medicamentos antes e durante a gestação; classes de medicamentos usados na gestação; tabagismo materno e paterno; etilismo materno e paterno; uso de drogas ilícitas pelos pais. Para a análise das informações, utilizou-se o modelo de regressão logística, além da razão de chances (OR) bruta e ajustada. Os resultados mostraram que, após os ajustes, foi encontrada associação entre o uso materno na gestação de antitérmicos/analgésicos (OR = 2,26; IC95% 1,29-3,95; p < 0,040) com o TEA. Já o uso de tabaco, álcool e drogas ilícitas materno e paterno, antes e durante a gestação, não apontou relação com o TEA. Os dados encontrados sugerem que existe influência de fatores ambientais no desenvolvimento do TEA.

Abstract The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.

Regulation of Redox Profile and Genomic Instability by Physical Exercise Contributes to Neuroprotection in Mice with Experimental Glioblastoma.

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training's effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.

BACKGROUND: Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality. METHODS: A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis. RESULTS: Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients. CONCLUSIONS: ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.

Effect of 3-Carene and the Micellar Formulation on Leishmania (Leishmania) amazonensis.

Leishmaniases are neglected tropical diseases caused by obligate intracellular protozoa of the genus Leishmania. The drugs used in treatment have a high financial cost, a long treatment time, high toxicity, and variable efficacy. 3-Carene (3CR) is a hydrocarbon monoterpene that has shown in vitro activity against some Leishmania species; however, it has low water solubility and high volatility. This study aimed to develop Poloxamer 407 micelles capable of delivering 3CR (P407-3CR) to improve antileishmanial activity. The micelles formulated presented nanometric size, medium or low polydispersity, and Newtonian fluid rheological behavior. 3CR and P407-3CR inhibited the growth of L. (L.) amazonensis promastigote with IC50/48h of 488.1 ± 3.7 and 419.9 ±1.5 mM, respectively. Transmission electron microscopy analysis showed that 3CR induces multiple nuclei and kinetoplast phenotypes and the formation of numerous cytosolic invaginations. Additionally, the micelles were not cytotoxic to L929 cells or murine peritoneal macrophages, presenting activity on intracellular amastigotes. P407-3CR micelles (IC50/72 h = 0.7 ± 0.1 mM) increased the monoterpene activity by at least twice (3CR: IC50/72 h >1.5 mM). These results showed that P407 micelles are an effective nanosystem for delivering 3CR and potentiating antileishmanial activity. More studies are needed to evaluate this system as a potential therapeutic option for leishmaniases.

Adjunctive effects of photodynamic therapy using indocyanine green in residual pockets during periodontal maintenance therapy: A split-mouth randomized controlled trial.

BACKGROUND: Prospective studies have reported conflicting results regarding the adjunctive effect of antimicrobial photodynamic therapy (aPDT) on clinical and microbiological parameters in individuals under periodontal maintenance therapy (PMT). This study aimed to evaluate the clinical and microbiological adjunctive effects of aPDT using indocyanine green (ICG) in residual sites with probing depth (PD) ≥5 mm during PMT in comparison with scaling and root planing (SRP) alone. METHODS: A split-mouth randomized controlled clinical trial was conducted with 24 individuals in a PMT program. Contralateral quadrants with eligible residual sites were randomly assigned to either SRP + aPDT (test group) or SRP alone (control). aPDT included ICG dye and diode laser (909 nm) performed together with SRP and repeated 15 days after. Periodontal clinical parameters, periodontal inflamed surface area (PISA) index, and subgingival biofilm samples were collected at baseline (T1), 3 (T2), and 6 months later (T3). Microbiological analyses were performed by quantitative real-time polymerase chain reaction. RESULTS: Significant improvements were observed in all clinical and microbiological parameters in both groups from T1 to T3. However, no significant differences were observed regarding plaque index, PD, and clinical attachment level. Test group showed significantly greater reductions in bleeding on probing (BOP), PISA index, and Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans levels, when compared with controls. CONCLUSIONS: Both treatments resulted in significant clinical periodontal improvements, but with no significant differences between groups except from inflammation parameters. aPDT using ICG resulted in significant reductions in BOP and PISA index, as well as in P. gingivalis and A. actinomycetemcomitans levels.

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or in vivo. Target finding strategies such as in silico modelling and mass spectroscopy hint towards a direct interaction between C1 and the nitric oxide synthase making C1 a great candidate for specific intra-cellular interaction with the NO producing machinery.

Thermosensitive system formed by poloxamers containing carvacrol: An effective carrier system against Leishmania amazonensis.

The drugs used in the treatment of leishmaniasis show problems concerning side effects and toxicity. As a result, the search for new actives is necessary, and natural products like carvacrol - 5-isopropyl-2-methylphenol, become a relevant alternative. To enable the use of carvacrol as an antileishmanial agent, thermosensitive hydrogels were developed from poloxamer triblock copolymers 407 (P407) and 188 (P188). Carvacrol-free and carvacrol-containing hydrogels were obtained from P407 alone and from the mixture of P407 and P188. The hydrogels were subjected to Differential scanning calorimetry, Small-angle X-ray scattering, Scanning electron microscopy, and Rheology analysis. The activity of hydrogels and carvacrol isolated against promastigotes and intracellular amastigotes of Leishmania amazonensis and their cytotoxicity in mammalian cells was determined. The sol-gel transition temperature for the binary hydrogel containing carvacrol (HG407/188CA) was 37.04 ± 1.35 °C. HG407/188CA presented lamellar structure at temperatures of 25 °C and 37 °C. HG407/188CA and carvacrol presented IC50 against Leishmania amazonensis promastigotes of 18.68 ± 1.43 µg/mL and 23.83 ± 3.32 µg/mL, respectively, and IC50 against Leishmania amazonensis amastigotes of 35.08 ± 0.75 µg/mL and 29.32 ± 0.21 µg/mL, respectively. HG407/188CA reduced the toxicity of carvacrol in all mammalian cells evaluated, raising the CC50 in murine peritoneal macrophages from 40.23 ± 0.21 µg/mL to 332.6 ± 4.89 µg/mL, obtaining a Selectivity Index (SI) of 9.5 against 1.37 of the isolated carvacrol. HG407/188CA provided higher selectivity of carvacrol for the parasite. Thus, the binary hydrogel obtained may enable the use of carvacrol as a potential antileishmanial agent.

Effect of supragingival plaque control on recurrent periodontitis and clinical stability among individuals under periodontal maintenance therapy: 10-year follow-up.

BACKGROUND: The aim of this study was to evaluate the effect of supragingival plaque control on the recurrence of periodontitis (RP) and the achievement of a stable periodontal clinical endpoint after 10 years of periodontal maintenance therapy (PMT). METHODS: The present retrospective cohort study included 225 individuals in continuous PMT. The plaque index (PI) determining the oral hygiene (OH) status, periodontal clinical parameters, and other variables of interest were collected at three time points: T1 (prior to active periodontal therapy [APT]), T2 (after APT), and T3 (10 years after T2). According to PI records at T3, participants were categorized into: (1) good OH (GOH; PI ≤ 30%, n = 63); (2) fair OH (FOH; PI > 30% and ≤40%, n = 73); and (3) poor OH (POH; PI > 40%, n = 88). Data were analyzed using the chi-square and Student t tests, analysis of variance (ANOVA), and mediation and regression analyses. RESULTS: Significant differences in all periodontal clinical parameters between the GOH, FOH, and POH groups were observed at T3. The POH group exhibited higher mean bleeding on probing (BOP), periodontal probing depth (PD), and clinical attachment level (CAL), as well as higher tooth loss (POH > FOH > GOH; P < .001). There was an increased risk for RP in the FOH (odds ratio [OR] 2.02; CI, 1.10-4.38) and POH (OR 4.33; CI, 2.17-8.65) groups. Moreover, the FOH and POH groups had an approximately 2.5 and 6.0 times greater chance of not achieving a stable periodontal clinical endpoint, respectively. CONCLUSIONS: After 10 years of monitoring in PMT, individuals with higher PI scores (>30%) presented an unhealthier periodontal status, a higher risk for RP, and a lower chance of achieving ≤4 sites with PD ≥ 5 mm.

Sedentary behavior in young adults using ecological momentary assessment: an image observation protocol / Comportamento sedentário em adultos jovens por avaliação momentânea ecológica: protocolo de observação por imagem

ABSTRACT New ways to obtain information on sedentary behavior (SB) have recently been explored. This study aimed at assessing the self-reported posture agreement by using the Ecological Momentary Assessment (EMA). The images were sent by an observation protocol created in a form that would be answered via the mobile phone of young adults. The bank of images was provided by 41 university students. Such images were obtained from a project carried out in 2019, which was based on the taxonomy of sedentary behavior. The following positions were assessed: sitting, lying/reclining and standing, comparing the images provided with the self-reported SB by using EMA, which was collected via cell phone. The agreement was assessed by two researchers independently. Data analysis was based on descriptive statistics, Student's t test, chi-squared test, and Cohen's k in SPSS 25 with P<0.05. The inter-rater reliability was strong/substantial, that is, 87.6% (rater 1; k = 0.696) and 88.6% (rater 2; k = 0.720). The image observation protocol created in an electronic form could discriminate the behavior adopted by the participants, as well as it could be used independently, only for recording EMA and/or the image/photograph.

RESUMO Novas formas de se obter informações sobre o comportamento sedentário (CS) têm sido exploradas recentemente. O objetivo do presente estudo foi verificar a concordância da postura auto-relatada por meio da Avaliação Momentânea Ecológica (AME). As imagens foram enviadas por meio de um protocolo de observação criado em um formulário respondido pelo telefone celular de adultos jovens. Foi utilizado um banco de imagens fornecido por 41 universitários, obtidas por um projeto realizado em 2019 com base na taxonomia do comportamento sedentário. As seguintes posições foram analisadas: sentada, deitado/reclinado ou em pé, comparando a imagem fornecida com o CS auto-reportado por meio da AME, que foi coletada por telefone celular. A concordância foi realizada por dois pesquisadores de modo independente. A análise dos dados foi realizada pela estatística descritiva, t de Student, qui-quadrado e k de Cohen no SPSS 25 com P<0,05. A concordância entre os avaliadores foi forte/substancial de 87,6% (avaliador 1; k = 0,696) e de 88,6% (avaliador 2; k = 0,720). O protocolo de observação por imagem criado por formulário eletrônico conseguiu discriminar o comportamento adotado pelos participantes, bem como viável de ser utilizado de modo independente, somente para o registro da AME e/ou da imagem/fotografia.

Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion.

Prion Diseases or Transmissible Spongiform Encephalopathies are neurodegenerative conditions associated with a long incubation period and progressive clinical evolution, leading to death. Their pathogenesis is characterized by conformational changes of the cellular prion protein-PrPC-in its infectious isoform-PrPSc-which can form polymeric aggregates that precipitate in brain tissues. Currently, there are no effective treatments for these diseases. The 2,5-diamino-1,4-benzoquinone structure is associated with an anti-prion profile and, considering the biodynamic properties associated with 4-quinolones, in this work, 6-amino-4-quinolones derivatives and their respective benzoquinone dimeric hybrids were synthesized and had their bioactive profile evaluated through their ability to prevent prion conversion. Two hybrids, namely, 2,5-dichloro-3,6-bis((3-carboxy-1-pentyl-4-quinolone-6-yl)amino)-1,4-benzoquinone (8e) and 2,5-dichloro-3,6-bis((1-benzyl-3-carboxy-4-quinolone-6-yl)amino)-1,4-benzoquinone (8f), stood out for their prion conversion inhibition ability, affecting the fibrillation process in both the kinetics-with a shortening of the lag phase-and thermodynamics and their ability to inhibit the formation of protein aggregates without significant cytotoxicity at ten micromolar.

Altered distribution and function of NK-cell subsets lead to impaired tumor surveillance in JAK2V617F myeloproliferative neoplasms.

In cancer, tumor cells and their neoplastic microenvironment can sculpt the immunogenic phenotype of a developing tumor. In this context, natural killer (NK) cells are subtypes of lymphocytes of the innate immune system recognized for their potential to eliminate neoplastic cells, not only through direct cytolytic activity but also by favoring the development of an adaptive antitumor immune response. Even though the protective effect against leukemia due to NK-cell alloreactivity mediated by the absence of the KIR-ligand has already been shown, and some data on the role of NK cells in myeloproliferative neoplasms (MPN) has been explored, their mechanisms of immune escape have not been fully investigated. It is still unclear whether NK cells can affect the biology of BCR-ABL1-negative MPN and which mechanisms are involved in the control of leukemic stem cell expansion. Aiming to investigate the potential contribution of NK cells to the pathogenesis of MPN, we characterized the frequency, receptor expression, maturation profile, and function of NK cells from a conditional Jak2V617F murine transgenic model, which faithfully resembles the main clinical and laboratory characteristics of human polycythemia vera, and MPN patients. Immunophenotypic analysis was performed to characterize NK frequency, their subtypes, and receptor expression in both mutated and wild-type samples. We observed a higher frequency of total NK cells in JAK2V617F mutated MPN and a maturation arrest that resulted in low-numbered mature CD11b+ NK cells and increased immature secretory CD27+ cells in both human and murine mutated samples. In agreement, inhibitory receptors were more expressed in MPN. NK cells from Jak2V617F mice presented a lower potential for proliferation and activation than wild-type NK cells. Colonies generated by murine hematopoietic stem cells (HSC) after mutated or wild-type NK co-culture exposure demonstrated that NK cells from Jak2V617F mice were deficient in regulating differentiation and clonogenic capacity. In conclusion, our findings suggest that NK cells have an immature profile with deficient cytotoxicity that may lead to impaired tumor surveillance in MPN. These data provide a new perspective on the behavior of NK cells in the context of myeloid malignancies and can contribute to the development of new therapeutic strategies, targeting onco-inflammatory pathways that can potentially control transformed HSCs.

Avaliação do microambiente alimentar em estabelecimentos fornecedores de alimentos em um município do trairí do Rio Grande do Norte / Evaluation of the food microenvironment in establishments supplying foods in acity of Trairi ofRio Grande do Norte / Evaluación del microambiente alimentario en provedores de alimentos en unmunicipio de Trairi doRio Grande do Norte

Introdução:As pessoas passaram a consumir alimentos prontos e ultraprocessados cada vez mais e diminuíram o consumo de alimentos naturais. Consequentemente, têm aumentado o desenvolvimento de obesidade e outras doenças crônicas não transmissíveis. Esse processo de transição nutricional e epidemiológico tem sido influenciado pelo ambiente alimentar. Objetivo:avaliar o microambiente alimentar em mercados e restaurantes do município de Santa Cruz, Rio Grande do Norte. Metodologia:Trata-se deuma pesquisa transversal e descritiva, de abordagem quantitativa, realizada em 60 estabelecimentos comerciais fornecedores de alimentos naturais, industrializados e refeições prontas. Foram aplicados questionários, de acordo com a classificação do tipo deestabelecimento para verificação da disponibilidade, variedade, preço e qualidade de alimentos naturais e ultraprocessados. Resultados:A maior parte dos estabelecimentos participantes eram mercados locais ou de bairros, localizados no centro da cidade, evidenciando as desigualdades territoriais.Foi visto que a disponibilidade de frutas e hortaliças era inferior aos ultraprocessados. Os alimentos apresentaram qualidade satisfatória e os menores preços de frutas foram encontrados nos supermercados e mercadinhos, enquanto os das hortaliças na feira livre. Conclusões:ficou evidente a necessidade de políticas públicas de incentivo a descentralização do comércio de alimentos e o incentivo à venda de alimentos mais saudáveis e acessíveis física e financeiramente (AU).

Introduction:People have started to consume more and more ready-to-eat foods and have reduced their consumption of fruit and vegetables. Consequently, the prevalence of overweight and chronic non-communicable diseases have increased over the years. This dietary and epidemiological transition process has been influenced by the food environment in which they are inserted. Objective:to evaluate the food microenvironment in markets and restaurants in the city of Santa Cruz, Rio Grande do Norte.Methodology:This is a cross-sectional and descriptive research, with a quantitative approach, carried out in 60 commercial establishments supplying natural and processed foods and ready-to-eat meals. Questionnaires were applied, according to the classification of the type of establishment, to check the availability, variety, price and quality of natural and ultra-processed foods.Results:Most of the participating establishments were local or neighborhood markets,located in the downtown, highlighting territorial inequalities. It was noted that the availability of fruits and vegetables is lower than the ultra-processed foods. All foods showed satisfactory quality, and the lowest prices for fruits were found in supermarkets and grocery stores, while vegetables were found in the street market. Conclusions:the need for public policies to encourage the decentralization of the food trade and the incentive to sell healthier and more affordable foodsphysically and financially became evident (AU).

Introducción: Las personas pasaron a consumir alimentos listos y ultraprocessados cada vez más y disminuyeron el consumo de alimentos naturales. Consecuentemente, las prevalencias de sobrepeso y enfermedades crónicas no transmisibles han aumentado con los años. Este proceso de transición alimentaria y epidemiológica ha sido influenciado por el entorno alimentario en el que se encuentran. Objetivo: evaluar el microambiente alimentario en mercados y restaurantes del municipio de Santa Cruz, Rio Grande do Norte.Metodología: Se trata de una investigación transversal y descriptiva, de abordaje cuantitativo, realizada en 60 establecimientos comerciales proveedores de alimentos naturales, industrializados y comidas preparadas. Se aplicaron cuestionarios de acuerdo con la clasificación del tipo de establecimiento para verificar la disponibilidad, variedad, precio y calidad de los alimentos naturales y ultraprocesados. Resultados: La mayor parte de los establecimientos participantes eran mercados locales o de barrios, localizada en el centro de la ciudad, destacando las desigualdades territoriales. Se ha visto que la disponibilidad de frutas y hortalizas es inferior a los ultraprocesados. Los alimentos presentaron calidad satisfactoria y los menores precios de frutas fueron encontrados en los supermercados y mercadillos, mientras que las hortalizas en la feria libre.Conclusiones: quedó evidente la necesidad de políticas públicas de incentivo a la descentralización del comercio de alimentos y el incentivo a la venta de alimentos más saludablesy asequibles física y financieramente (AU).

Human induced pluripotent stem cell engineering establishes a humanized mouse platform for pediatric low-grade glioma modeling.

A major obstacle to identifying improved treatments for pediatric low-grade brain tumors (gliomas) is the inability to reproducibly generate human xenografts. To surmount this barrier, we leveraged human induced pluripotent stem cell (hiPSC) engineering to generate low-grade gliomas (LGGs) harboring the two most common pediatric pilocytic astrocytoma-associated molecular alterations, NF1 loss and KIAA1549:BRAF fusion. Herein, we identified that hiPSC-derived neuroglial progenitor populations (neural progenitors, glial restricted progenitors and oligodendrocyte progenitors), but not terminally differentiated astrocytes, give rise to tumors retaining LGG histologic features for at least 6 months in vivo. Additionally, we demonstrated that hiPSC-LGG xenograft formation requires the absence of CD4 T cell-mediated induction of astrocytic Cxcl10 expression. Genetic Cxcl10 ablation is both necessary and sufficient for human LGG xenograft development, which additionally enables the successful long-term growth of patient-derived pediatric LGGs in vivo. Lastly, MEK inhibitor (PD0325901) treatment increased hiPSC-LGG cell apoptosis and reduced proliferation both in vitro and in vivo. Collectively, this study establishes a tractable experimental humanized platform to elucidate the pathogenesis of and potential therapeutic opportunities for childhood brain tumors.